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BIO LCV: NERVOUS SYSTEM M. SAUMIER Overview: Divided into Central Nervous System (Brain and Spinal Cord) and Peripheral Nervous System (Afferent and Efferent divisions consisting of cranial and spinal nerves). Receptor->Sensory (Afferent) division ->Central Nervous System ->Motor (Efferent) Division-> Somatic Nervous System (Voluntary, Skeletal Muscle) or -> Autonomic Nervous System (Involuntary) : Sympathetic Nervous System, Parasympathetic and Enteric Nervous System -> Effector (Muscles or Glands) Receptors: Detect changes in external environment (Exteroreceptors) photoreceptors in retina of the eye (Electromagnetic receptor) taste buds ( Chemoreceptor) In skin : Heat, cold, light touch, pressure and pain receptors) or internal environment (Interioreceptors) proprioreceptor (muscles and tendons stretching) blood pressure monitor Microscopy: Nervous tissue is composed of 2 major types: Neurons (Nerve cells) and neuroglial cells (or glial cells, smaller and more numerous, supporting neurons). There are 6 types of Neuroglial cells (4 in CNS and 2 in PNS). Neuroglial cells in CNS are: Astrocytes, Microglia, Ependymal cells and Oligodendrocytes. In the PNS, neuroglial cells are Sattelite and Schwann cells. 1. Astrocytes (Star shaped): Most numerous and versatile; support and anchor neurons; cling to neurons and neighboring capillaries to provide nutrients to neurons; help form the Blood-Brain Barrier by forming tight junctions between endothelial cells that lines the capillaries; provides proper environment for nerve impulse conduction (monitor calcium and potassium concentrations); remove excess neurotransmitter; guide neuron’s migration into forming synapses during brain development. 2. Microglial cells: Immune System type of function (special macrophage because of the Blood-Brain Barrier); phagocytize microbes; remove debris of dead cells; migrates to area of injured neurons. 3. Ependymal cells: (squamous or columnar, some are ciliated) Line ventricles of the brain; produce cerebrospinal fluid and help in the circulation of this fluid. 4. Oligodendrocytes: Forms myelin sheath around axons of neurons in CNS in the white matter. 5. Sattelite cells: Surround neuron cell bodies within ganglia, function unclear. 6. Schwann cells: Surround and form myelin sheaths around large neurons in PNS. They insulate, increase speed of nerve impulse (Saltatory Conduction) and are vital to regeneration of peripheral nerve processes. The exposed outer portion of the Schwann cell is called neurolemma. The myelin sheaths do not touch each other and the neuron is exposed at the Nodes of Ranvier Neurons: Structural unit; specialized in nerve impulse conduction; extreme longetivity, amniotic (no centrioles) except olfactory epithelium and hypoccampus (learning, memory) has stem cells; high metabolic activity, high demand in glucose and oxygen. Composed of a cell body, dendrites and axon. 1. Cell body contains nucleus with visible nucleolus and other organelles. Rough Endoplasmic Reticulum, called Nissl bodies, is active and well developed to make neurotransmitters. Most cell bodies of neurons are located in the gray matter or nuclei of the CNS or in ganglia in PNS. Two types of processes extend from the cell body called dendrites and axons. Bundles of processes in the CNS are called tracts and in the PNS are called nerves. 2. Dendrites are input regions detecting stimuli and conducting message towards cell body (not as an action potential but as a graded potential) and are numerous in a multipolar neuron. 3. A single axon originates from the cell body at a cone-shaped area called an axon hillock and may branch into axon collaterals. Axon terminates into terminal branches or telodendria each ending into a knoblike secretory (neurotransmitter) structure called axonal terminals or synaptic end bulbs or boutons. Axon generates and conducts nerve impulses away from the cell body. Axons contain same organelles as cell body and dendrites except Nissl bodies and Golgi apparatus and therefore need cell body for manufacturing neurotransmitters and proteins (cytoskeleton, motor proteins) involved in the transport of vesicles containing neurotransmitter to the synaptic end bulbs (anterograde movement). Movement occurs in both directions, for example damaged organelles are returned to the cell body (retrograde movement) and other clues aid in communication with the cell body to indicate health of the axon to stimulate the release of growth factors. Unfortunately viruses (polio, rabies, herpes) or tetanus toxins can use the retrograde movement to attack the cell body. Axon can be wrapped by myelin sheath which insulates the neuron. Classification of Neurons: Structural: Multipolar, Bipolar, unipolar. Functional: Sensory, Motor, Interneuron. 1. Multipolar neurons: Most common, 3 or more processes. 2. Bipolar neurons: 2 processes; one axon and one dendrite. Rare and only in special sense like in receptor cells in retina (rods, cones) and olfactory epithelium. 3. Unipolar neurons: One process that leaves cell body and divides into peripheral and central processes. Since both conduct impulses they can be referred as axon but the tip of the peripheral process has receptors 4. Sensory (afferent) neurons: Transmit impulses from receptors in skin or viscera to CNS. Most are unipolar but some are bipolar in the special senses. 5. Motor (efferent) neurons: Carry impulses away from CNS to the effectors. All are multipolar and most have their cell body in the gray matter of the CNS (except some in the ANS). 6. Interneurons (association neurons): Located in between sensory and motor neurons to carry information (nerve impulse) for integration. Most numerous type in NS and most are multipolar. Central Nervous System (CNS): Spinal Cord and Brain: CNS is surrounded by meninges: 3 layers: Dura mater (Tough mother, outer, dense irregular connective tissue), Arachnoid (delicate web of collagen and elastic fibers) and Pia mater (delicate mother, inner, adheres to CNS, transparent). The epidural space is located between vertebral column/cranial bones and the Dura Mater, site of epidural block (labor pain). The subarachnoid space is situated between the arachnoid and pia mater and is where the cerebrospinal fluid (CSF) circulates around the spinal cord and the brain, site of spinal tap or lumbar puncture (removing CSF, intro antibiotics, anesthetics, chemotherapy). Spinal Cord: Function: Highway for nerve impulse conduction: sensory (from PNS to brain) and motor (brain to PNS) in the white matter and integration of incoming and outgoing information in gray matter (spinal reflex). Anatomy: Length from occipital bone (cranium) to the second lumbar vertebrae, ends in a horse tail-like of nerves called cauda equina. Two enlargements: cervical enlargement (nerves to arms) and lumbar enlargement (nerves to legs). Encased within a vertebral column composed of vertebrae called by regions (cervical, thoracic, lumbar, sacral), 31 spinal segments where a pair of spinal nerves originate from a dorsal root and ventral root merging at the intervertebral foramina. Both roots come from the spinal cord and fuse to form a spinal nerve which is mixed (Sensory and motor). Spinal nerve can divide into several rami (ramus) which can form a network called plexus. The dorsal root has a dorsal root ganglion where the cell bodies of sensory (afferent, unipolar) neuron are located. The ventral root is composed of axons from motor (multipolar efferent) neurons. Cross-section: Two grooves (anterior median fissure and posterior median sulcus), a H – shaped gray matter inside where cells bodies of motor neurons and interneurons are located (anterior gray horns, posterior gray horns) and white matter outside composed of myelinated and unmyelinated axons of ascending tracts (sensory) and descending tracts (sensory) (in anterior, lateral, posterior white columns). A central canal located in the center of the gray matter where CSF circulates. Spinal Reflexes: Pathway called reflex arc, quick automatic response to sensory impulse coming in via spinal nerves, integration in gray matter. Composed of sensory receptor, sensory neuron (axon terminates in gray matter), integrating center (synapses between sensory and motor or interneurons required), motor neuron and effector (muscle or gland). Somatic Reflexes involve involuntary skeletal muscles eg. Patellar reflex (knee jerk reflex), withdrawal reflex prevents limbs from getting serious injuries. Brain: It becomes one of the largest organ of the body (needs 20% of oxygen), divided into 4 parts: 1. Brain Stem (Medulla Oblongata, pons, midbrain) 2. Diencephalon (Thalamus, Hypothalamus, epithalamus) 3. Cerebrum (2 cerebral hemispheres, cerebral cortex) 4. Cerebellum. 1. Brain Stem: Medulla Oblongata : is located superior to the spinal cord, contains all sensory (ascending) and motor (descending) tracts (white matter) from spinal cord to other parts of the brain. Anterior surface bulges to form pyramids where most tracts on the right side cross over to the left, and the tracts on the left cross over to the right in region called decussation of pyramids (one side of the brain controls the other side of the body). Contains nuclei controlled by the ANS: Cardiovascular center (heart rate, stroke volume, diameter of arterioles), medullary rhythmicity area (rhythm of breathing) and other centers (reflexes for swallowing, vomiting, coughing, sneezing). Pons: Bridge, superior to Medulla Oblongata, inferior to Midbrain and anterior to cerebellum. Tracts connect spinal cord to brain or brain parts together (relay information between cerebral cortex and cerebellum). Nuclei that help regulate the normal rhythm of breathing (with the Medulla) and nuclei of some cranial nerves. Midbrain: Located in between the pons and Diencephalon, contains cerebral peduncles , a pair of motor (from cerebral cortex to pons/spinal cord) and sensory tracts (spinal cord to thalamus). Nuclei of two cranial nerves. Inferior (auditory) and superior (visual) colliculi. Reticular Formation: Throughout brain stem and diencephalons, diffused network of neurons and clusters of cell bodies (gray matter). Sensory filter that alerts cerebral cortex of incoming sensory information. Helps regulate muscle tone (motor). RAS (Reticular Activating System) regulates sleep and arousal cycle. 2. Diencephalon: Thalamus: Located above the midbrain, Egg-shaped, composed of a mass of nuclei (gray matter), gateway to the cerebral cortex: it is the major relay station of sensory info from the spinal cord, brain stem, cerebellum and parts of the cerebrum to the cerebral cortex (consciousness). Allows for crude recognition of sensory info (pleasant, unpleasant) like pain, temperature, pressure. Plays role in awareness (screens calls, sorts and edits info) and acquisition of knowledge (learning, memory: cognition). Hypothalamus: Located below thalamus and above the pituitary gland, small but very important job of watchdog (homeostasis) or master gland? -Controls and integrates activities of ANS such as heart rate, blood pressure, movement of food throughout the GI tract, respiratory rate and depth, pupil size and contraction of the urinary bladder (by controlling the centers in the brain stem). -Controls the release of hormones from the anterior lobe of the pituitary gland (controls endocrine system) and makes and secretes 2 hormones in the posterior lobe of the pituitary gland (endocrine function). -Regulates emotions (and physical expression of emotions via ANS) like rage, aggression, pain and pleasure (with limbic system) and behaviors such as sex drive. -Regulates food intake via changing glucose or amino acids concentrations in blood (feeding and satiety centers) and drinking via a decrease in blood volume (thirst center). -Controls body temperature (thermostat) eg. Sweating or shivering. -Regulates circadian rhythms and state of consciousness (awake/sleep pattern). Stimulates the Reticular Activating System (RAS) which stimulates the cortical activity and therefore consciousness. Biological clock: Hypothalamic Suprachiamatic Nuclei (SCN) uses external cues like light intensity, synchronize with environmental cycles. (if not 24 hours and 11 minutes) Epithalamus: most dorsal portion of diencephalons forms roof of third ventricles containing a choroids plexus which form Cerebrospinal Fluid (CSF). Pineal gland increase secretion of melatonin at night for sleep. (malfunctioning: SAD, insomnia, Jet lag, depression) . 3. Cerebrum: Gray matter on the outside forming cerebral cortex grew faster than underneath white matter forming folds (gyri) and grooves (deep: fissures, shallow: sulci). The longitudinal fissure separates the cerebrum into right and left cerebral hemispheres which are connected by white matter called the corpus collosum. The neocortex consists of 6 layers of neurons having large surface area associated with intergration (association areas). The transverse cerebral fissure separates the cerebrum from the cerebellum. Basal ganglia are located in the white matter and are responsible for control of large subconscious movements of skeletal muscles: swinging arms during walking, adjustment of muscle tone required during movement. Damage to basal ganglia can result in tremor, stiffness and involuntary movements like in Parkinson’s disease. Functional Areas of the Cerebral Cortex: Each cerebral hemisphere is divided into 4 lobes: 1.Frontal Lobe (Primary Motor cortex) 2. Parietal Lobe (Somatosensory:sensory cortex) 3. Temporal Lobe (Auditory) 4. Occipital Lobe ((Visual ) The cerebral cortex is divided into three functional areas: sensory, association and motor. Sensory Areas located in posterior half receives and interprets sensory impulses. Primary Somatosensory Area (1, 2, 3) receives info from touch, proprioception (limb position), pain, temperature. Primary Visual Area (17) on occipital, receives visual info (shape, color, movement). Primary Auditory Area (41,42) on temporal lobe, receives sound (hearing) impulses as pitch and rhythm. Wernicke area: Located in posteroior temporal lobe, responsible for the ability to comprehend speech. Primary Gustatory Area (43) receives info from taste buds. Primary Olfactory Area (28) receives impulse from smell. Motor (muscular movement) areas: Located on both hemispheres(left side controls right side of body and vice versa), posterior portion of frontal lobe, more cortical area is taken for higher degree of precision of movements: fingers, talking (lips, tongue, vocal cords). Primary motor area (4): Controls specific muscles or group of muscles. Motor neurons of the same area can innervate a series of muscles that work in synergy to perform a precise sequence of movement. Premotor area (6): Controls learned motor skills of a repetitious or patterned nature like a “memory bank for skilled motor activities”eg: typing, writing a word, playing musical instrument Broca’s speech area (44, 45): Special motor area that controls muscles involved with generating speech, also active when preparing (planning) speech. Frontal eye field controls voluntary eye movement. Association areas: (Integrative) Responsible for memory, emotions, reasoning, will, judgment, personality traits, intelligence, consist of motor and sensory areas and located on the lateral sides of the occipital, parietal, temporal lobes and anterior to motor area on frontal lobe. Somatosensory association area (5, 7) integrate and interpret somatic sensations, storage of memories of past sensory experiences (recognize object by touching without seeing). Visual Association Area (18, 19) on the occipital lobe, recognizes and evaluates what is observed, using present and past visual experiences. Auditory Association Area (22) located on temporal lobe, responsible in discriminating sounds, recognition of if it is speech, music or noise, stores memories of sounds. Wernicke’s area (22, 39, 40) formerly believed to be responsible for comprehending written or spoken language, now believed to be involved with sounding out unfamiliar words. General (common) interpretation area, not well defined and area smaller than once thought, usually on the left hemisphere only. Receives info from all sensory areas and integrates into a single thought or understanding. Visceral Association Area: Conscious perception of sensations of organs eg. Full bladder, upset stomach. Hemisphere Lateralization: Physically both hemispheres are symmetrical but some people use one hemisphere more than the other. 2/3 of the population have a larger area for the Wernicke’s on the left hemisphere. In most, the left hemisphere is more involved with spoken and written language, mathematical, scientific skills, logic and reasoning. The right hemisphere is more important in art, pattern perception, recognition of faces and emotion, Nonverbal thinking (mental images of sight, sound, touch, taste and smell). Differences between hemispheres are less pronounced in woman. Females have a larger corpus callosum than males and might explain why we are usually better at expressing our emotions. Emotions: Limbic System consists of 3 parts in the Cerebral cortex forming a ring around the Brainstem: Amygdala Hyppocampus Olfactory bulb Inner portion involving Thalamus and Hypothalamus (primary emotions; laughing and crying) and Brainstem (aggression, feeding, sexuality, nurturing and bonding). Memory/ learning: Ability to recall thought and information, essential for learning, use our experience, part of our consciousness. Located in various parts of the brain: association area of the frontal, parietal, occipital and temporal lobes, portion of limbic system (hypocampus) and diencephalon. Two stages: Short-term (STM) and Long-term (LTM) memories. STM limited to 7-8 chunks of information (phone number you just looked-up, sequence of words) and temporary holding bin (cramming exam material that you forget hopefully after exam). It takes time to transfer STM to LTM for memory to become permanent. LTM involves cellular mechanisms, has a limitless capacity, continually changing memory bank, but the ability to store or retrieve info declines with aging. The transfer of info from STM to LTM depends on: Emotional state (requires hippocampus) (learning best when aroused or stressed because of Norepinephrine) Rehearsal (repeat), Association (relating to old info Automatic (unconscious record of info). Fact memory is stored in context, associated with thoughts, ability to work with symbols and language. Skill memory is less conscious, involves motor activities and is acquired through practice, once learned hard to unlearn (riding bike, tying shoes). Specific pieces of memories are stored where one would need to recall them eg. Visual memory are stored in the occipital lobe, musical memory on temporal lobe. Memory is difficult to study (Creates a physical change in the CNS), info known when learning: type of RNAs present altered, delivered to axon and dendrites, dendrite’s shape modified, unique extracellular proteins are secreted at synapses in LTM, number and size of synaptic end bulbs are increased (presynaptic neuron), more neurotransmitters are secreted, new neurons in hypocampus are formed. Memory formation involves circuits formed between the cortical sensory area, Amygdala and hypocampus, Diencephalon, prefrontal cortex , to basal forebrain back to sensory cortex where memory loop is closed. Brain Wave and EEG: Reflects continual electrical activity of the cerebral cortex, amplitudes reflects number of neurons carrying impulses (low during awake state, high during sleep), translated into unique individual patterns recorded as brain waves. Grouped into 4 categories depending on their frequencies (hertz = peaks/seconds): Alpha waves: regular and rhythmic, low-amplitude “idling brain: calm, relaxed state of wakefulness. Beta waves: irregular rhythmic, higher frequency: mentally alert, concentrated, solving a problem, visual stimulation. Theta waves: more irregular, common in children, abnormal in awake adults. Delta waves: high-amplitude, during sleep, anesthesia, brain damaged awake adults. Disorder: Epilepsy, petit mal, grand mal/ aura. Sleep-Awake Cycles: State of partial unconsciousness, decreased activity of the cerebral cortex, environment monitoring (sleepwalking), brainstem function for vital reflexes, can be aroused by stimulation. Two types that alternate: Non-rapid eye movement (NREM) and Rapid eye movement (REM, like the band) sleeps. Start sleep with going through 4 stages of NREM -> EEG becomes irregular and backtrack NREM stages to1 -> REM (after 1 ½ hour of sleep), Dreaming: EEG show alpha waves (aroused state), brain’s oxygen demand greater than when awake, increases in body temperature, heart and respiratory rates, blood pressure, erection in man and decrease in GI tract motility, rapid eye movements under lids, paralysis of skeletal muscles (limbs) so we don’t act out or dreams. After REM, descent to stage 4 of NREM. During sleeping, alternate back and forth between NREM and REM. Each period of REM increases as the night goes on (from 5 minutes to 50 minutes, total ½ the sleep in infant and 25% in adults) and therefore the longest dream is before you wake-up. Note: Most nightmares occur during stage 3 and 4 of NREM. RAS is responsible for awake/conscious state, sleeping pattern, especially dreaming and waking up. Stage 4 (slow –wave sleep, winding down) is important restorative properties. REM might be important occasion to review (analyze) the events of the day, lack of REM sleep makes you moody, depressed. Alcohol and sleep medications suppress REM sleep. Sleeping disorders: Narcolepsy, Insomnia, Sleep apnea. 4. Cerebellum: Anatomy: Cauliflower-like, dorsal to pons, 2 cerebellar hemispheres connected by vermis, thin outer cortex layer of gray matter, internal tree-like white matter (arbor vitae “tree of life”), Cerebellar Peduncles connect cerebellum to Brain Stem, no direct connection to cerebral cortex . Functions: Role in cognition, languages and problem solving. Recognize and predict sequences of events, adjust multiple forces applied on limbs, joints. Involved in learning and remembering motor skills (riding a bike) Balance and posture: Provides subconscious precise timing and proper pattern of skeletal muscle contractions for coordination, agility, driving, riding a bike, typing, playing a musical instrument. Receives info from proprioreceptors (tension of tendons and skeletal muscles, joint position), visual and equilibrium (see notes 8). Communicates to cerebral motor cortex the info on coordination of a movement. Intergrates sensory info from surrounding needed in hand-eye coordination Impeded with alcohol. Drunk test of touching nose or walking in a straight line. Neurotransmitters: Acetylcholine (ACh) Excitatory to skeletal muscles. Excitatory or inhibitory to other sites (Parasympathetic Nervous System) Norepinephrine (derived from tyrosine, an amino acid)CNS and PNS (Sympathetic Nervous System) Dopamine and Serotonin (derived from the amino acid tryptophan) affect sleep, mood, attention and learning. Endorphins natural analgesics Cerebrospinal Fluid (CSF) Circulation: Liquid cushion, helps feed brain, carries chemical signals (hormones and sleep- and appetite- inducing) all around the CNS (brain and spinal cord). Cerebrospinal fluid has similar composition than plasma (blood) except less proteins and different ion concentrations (more sodium, chloride and hydrogen ions, pH). Choroid plexuses composed of ependymal cells (neuroglial cells, tight junction, ion pumps) located at roof (ceiling) of each 4 ventricles, filter blood, form ion gradient for osmosis of fluids into ventricles, remove waste products (CSF replaced every 8 hours). Movement of CSF through all ventricles caused by cilia of ependymal cells, through central canal of spinal cord, in subarachnoid space all around CNS and returns to blood in dural sinuses via arachnoid villi. Disorder: Hydrocephalus (“water on the brain”). Autonomic Nervous System (ANS): Involuntary control of smooth, cardiac muscles and glands to regulate blood flow, heart rate, blood pressure, body temperature, stomach secretions to maintain the state of homeostasis. Composed of two divisions: Parasympathetic and Sympathetic divisions which innervate same organs (heart, lungs, digestive system, excretory system etc) but do opposite effects (sympathetic innervates more: smooth muscles of arteries and veins, glands (sweating). Function: Parasympathetic Division: Body maintenance; resting, digestion, elimination (feces, urine), decreases heart and respiratory rates, blood pressure, pupil constricted. Sympathetic Division: Fight-or Flight, activated when excited, exercising, embarrassment or emergency situation (response to threat, pounding heart, rapid deep breathing, bronchioles dilate, liver releases more glucose into blood for more energy, sweaty skin, dilated pupils, GI tract motility decreased. Anatomy: Anatomical differences between the two divisions: Different origins: Parasympathetic begins at brainstem (Vagus nerve originates from nuclei in medulla) and sacral portion of spinal cord, Sympathetic emerge from thoracic and partly lumbar regions of spinal cord. Different lengths of pre- and postganglionic neurons: parasympathetic has long preganglionic and short postganglionic neurons. Sympathetic has short preganglionic and long postganglionic neurons. Location of ganglia: Most parasympathetic ganglia are located near or in effector organs, sympathetic ganglia located near spinal cord in a sympathetic trunk (on both sides). Differences in neurotransmitter released: Acetylcholine (Ach) is released by all preganglionic neurons and parasympathetic postganglionic neurons. Most sympathetic postganglionic neurons release norepinephrine (NE).